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首页> 外文期刊>Cellular Signalling >Regulation of the methylation status of G protein-coupled receptor kinase 1(rhodopsin kinase)
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Regulation of the methylation status of G protein-coupled receptor kinase 1(rhodopsin kinase)

机译：G蛋白偶联受体激酶1（视紫红质激酶）甲基化状态的调节

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Rhodopsin kinase(GRK1)is a member of G protein-coupled receptor kinase family and a key enzyme in the quenching of photolysed rhodopsin activity and desensitisation of the rod photoreceptor neurons. Like some other rod proteins involved in phototransduction, GRK1 is posttranslationally modified at the C terminus by isoprenylation(farnesylation), endoproteolysis and α-carboxymethylation. In this study, we examined the potential mechanisms of regulation of GRK1 methylation status, which have remained unexplored so far. We found that considerable fraction of GRK1 is endogenously methylated. In isolated rod outer segments, its methylation is inhibited and demethylation stimulated by low-affinity nucleotide binding. This effect is not specific for ATP and was observed in the presence of a non-hydrolysable ATP analogue AMP-PNP, GTP and other nucleotides, and thus may involve a site distinct from the active site of the kinase. GRK1 demethylation is inhibited in the presence of Ca ~(2+)by recoverin. This inhibition requires recoverin myristoylation and the presence of the membranes, and may be due to changes in GRK1 availability for processing enzymes upon its redistribution to the membranes induced by recoverin/Ca ~(2+). We hypothesise that increased GRK1 methylation in dark-adapted rods due to elevated cytoplasmic Ca ~(2+)levels would further increase its association with the membranes and recoverin, providing a positive feedback to efficiently suppress spurious phosphorylation of non-activated rhodopsin molecules and thus maximise senstivity of the photoreceptor. This study provides the first evidence for dynamic regulation of GRK1 α-carboxymethylation, which might play a role in the regulation of light sensitivity and adaptation in the rod photoreceptors.
机译：视紫红质激酶（GRK1）是G蛋白偶联受体激酶家族的成员，是光解视紫红质活性和杆感光细胞神经元脱敏的关键酶。像其他一些涉及光转导的棒蛋白一样，GRK1在C末端通过异戊烯基化（法呢基化），内蛋白水解和α-羧甲基化进行了翻译后修饰。在这项研究中，我们研究了调节GRK1甲基化状态的潜在机制，至今尚未探索。我们发现GRK1的相当一部分是内源甲基化的。在分离的杆外部区段中，其低亲和力核苷酸结合会抑制其甲基化并促进去甲基化。这种作用对ATP不是特异的，并且在存在不可水解的ATP类似物AMP-PNP，GTP和其他核苷酸的情况下观察到，因此可能涉及一个不同于激酶活性位点的位点。在钙〜（2+）存在下，Recoverin可以抑制GRK1脱甲基。这种抑制作用需要恢复蛋白肉豆蔻酰化和膜的存在，并且可能是由于在由恢复蛋白/ Ca〜（2+）诱导的膜重新分布到膜上时，GRK1可用于处理酶的能力发生了变化。我们假设，由于细胞质Ca〜（2+）水平升高，暗适应棒中的GRK1甲基化增加，将进一步增加其与膜和recoverin的缔合，从而提供了积极的反馈，可有效抑制未激活的视紫红质分子的假磷酸化，因此最大化感光器的灵敏度。这项研究提供了动态调节GRK1α-羧甲基化的第一个证据，这可能在杆感光器的光敏性和适应性调节中起作用。

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